Two approaches to the study of morphine addiction, tolerance, and withdrawal are described which examine the anatomical and physiological effects of both acute and chronic morphine administration. The first series of experiments deals with the effects of morphine administration on hypertrophy of astroglia and proliferation of microglia in brain. Preliminary results suggest that certain brain regions are differentially responsive to acute morphine administration with respect to microglial proliferation. These findings will be investigated further employing techniques that have been utilized to study other forms of anatomical plasticity resulting from different forms of physical insult. The second approach seeks to establish a reliable in vitro test system delineating the physiological changes in nerve cells that accompany morphine administration, tolerance, and withdrawal. Initial experiments will seek to characterize the nature of these physiological changes in terms of effects on pre- and postsynaptic factors accompanying acute and chronic morphine administration to intact brain slices.